The present invention involves a process for direct resolution of 6-oxo-2-piperidinecarboxylic acid enantiomer mixtures using quinine as the resolving agent to obtain the individual d and l isomers.
The preparation of the d isomer of 6-oxo-2-piperidinecarboxylic acid (piperidone carboxylic acid) is reported in Journal of the American Chemical Society 75, 1994-1995 (1953). The process consists of three steps, namely chloroacetylation of dl .alpha.-amino adipic acid enzymatic resolution of the chloroacetyl-dl-.alpha.-aminoadipic acid and finally, cyclization of the individual isomer to prepare the cyclic d 6-oxo-2-piperidinecarboxylic acid. In addition to involving three steps, the enzyme resolution step is very difficult and unreliable.
A simpler procedure for obtaining the individual d or l isomer of 6-oxo-2-piperidinecarboxylic acid has been discovered, which is more direct and does not require the difficult enzyme resolution. This simple procedure involves resolution of e.g. d,l-6-oxo-2-piperidine carboxylic acid by salt formation with quinine and recovering the individual enantiomer from the diastereo isomer salt directly.